A site-specific antibody produced with a novel immunization procedure by induction of tolerance to cross-reacting determinants and its utilization in clinical research.

在这项研究中，开发和利用了一种新的免疫程序，以产生具有临床意义的配体的位点特异性抗体，具有低交叉反应性。该方法包括通过用交叉反应决定簇-D-G1缀合物处理动物并用含有必需决定簇的配体免疫来诱导B淋巴细胞对所述配体分子上的交叉反应决定簇的耐受性。1.利用该免疫程序成功地诱导了CCK-8特异性抗体，发现该抗体检测具有生物活性的CCK本身，而不检测CCK-前体和CCK-降解物。2.用CCK-8特异性抗体检测CCK-8，发现CCK广泛分布于中枢神经系统中，除初级感觉神经元外，还包括中脑多巴胺神经元及其投射区。此外，颈拳组大鼠大脑颞、顶、枕皮质CCK水平明显降低 ...更多信息 ULA犬和二甲基亚硝胺处理的犬，其制备为肝性脑病的实验模型。苯丙氨酸和酪氨酸在这些动物的皮质中增加。CCK的降低与芳香族氨基酸的增加无相关性。因此，这些结果意味着CCK水平的降低是通过与诱导假神经递质增加不同的机制引起的。3.首先通过使用上述设计的免疫程序开发神经激肽A和神经激肽B特异性抗体。使用这些特异性抗血清的放射免疫测定使我们能够直接测量这些神经激肽。测定大鼠不同脑区和脊髓中的免疫反应性神经激肽A和B，发现它们以不同的比例存在，这取决于区域。4.通过利用新的免疫程序，我们试图建立以下位点特异性抗体：抗体，使我们能够区分A和B等位基因的人葡萄糖-6-磷酸脱氢酶，抗体，使我们能够区分肿瘤相关的变化在糖部分的人绒毛膜促性腺激素。少

In this study, a novel immunization procedure to produce a site-specific antibody to a ligand of clinical significance with low cross-reactivity was developed and utilized. the method involved the induction of B-lymphocyte tolerance to the cross-reacting determinants on molecules of the ligand in question by treatment of animals with the cross-reacting determinant-d-gl conjugate and immunization with the ligand containing the requisite determinants. 1. Cholecystokinin (CCK)-8-specific antibody was successfully induced by using this immunization procedure, and it was found that the antibody detects biologically active CCK itself but not CCK-precursor and CCK-degradates. 2. By using this CCK-8-specific antibody, CCK was found to widely distribute in central nervous system, except primary sensory neurons, including mesencephalic dopamine neurons and in their projection areas. In addition, CCK levels were significantly reduced in temporal, parietal and occipital cortex of brain of eck fist … More ula dogs and dimethylnitrosamine-treated dogs which were prepared as experimental models of hepatic encphalopathy. Phenylalanine and tyrosine were increased in cortex of these animals. Amounts of reduction of CCK, however, did not correlate with those of increment of the aromatic amino acids in cortex of these models. Thus, these results imply that reduced levels of CCK are elicited by the mechanism distinct from that inducing increase of false neurotransmitter. 3. Neurokinin A- and neurokinin B-specific antibodies were firstly developed by using the abovedevised immunization procedure. Radioimmunoassays using these specific antisera allowed us to measure these neurokinins directly. Measurements of immunoreactive neurokinin A and B in different rat brain regions and spinal cord revealed that they are present with various ratios depending on the region. 4. By utilizing the novel immunization procedure, we are trying to establish the following sitespecific antibodies: antibodies which enable us to distinguish A and B allele of human glucose-6-phosphate dehydrogenase, and antibodies which enable us to distinguish the tumor-related change in in sugar moiety of human choriogonadotropin. Less